Alterations in synaptic plasticity coincide with deficits in spatial working memory in presymptomatic 3xTg-AD mice.
Alterations in synaptic plasticity coincide with deficits in spatial working memory in presymptomatic 3xTg-AD mice.
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DOI：
10.1016/j.nlm.2015.09.003
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发表时间：
2015-11
影响因子：
2.7
通讯作者：
Wagner JJ
中科院分区：
文献类型：
--
作者：
Clark JK;Furgerson M;Crystal JD;Fechheimer M;Furukawa R;Wagner JJ
阿尔茨海默病是一种神经退行性疾病，被认为是由淀粉样蛋白-肽的产生引起的，淀粉样蛋白-肽导致突触功能障碍和进行性记忆丧失。采用8臂放射状迷宫法对小鼠阿尔茨海默病（3xTg-AD）模型进行空间工作记忆评估。出乎意料的是，与年龄匹配的非tg对照动物相比，年龄较小（3个月大）的3xTg-AD小鼠在空间工作记忆任务中的受损程度与年龄较大（8个月大）的3xTg-AD小鼠一样。获取腹侧海马切片CA1区的场电位记录，以评估突触传递和突触可塑性能力。3月龄时，3xTg-AD小鼠LTP中NMDA受体依赖成分减少。然而，LTP的非nmda受体依赖性成分的大小同时增加，导致3xTg-AD和非tg小鼠的总LTP量相似。8月龄时，3xTg-AD小鼠的NMDA受体依赖性LTP再次减少，但非NMDA受体依赖性成分也减少，导致3xTg-AD小鼠的LTP总量明显低于非NMDA小鼠。3和8个月大的3xTg-AD小鼠均表现出成对脉冲促进和NMDA受体依赖性LTP的减少，这与空间工作记忆的缺陷相一致。这种认知障碍的早期存在和突触可塑性的相关改变表明，在阿尔茨海默病3xTg-AD小鼠模型中，在可检测到斑块和缠结存在之前，一些行为和神经生理学后果的发生可能发生。
Alzheimer's disease is a neurodegenerative condition believed to be initiated by production of amyloid-beta peptide, which leads to synaptic dysfunction and progressive memory loss. Using a mouse model of Alzheimer's disease (3xTg-AD), an 8-arm radial maze was employed to assess spatial working memory. Unexpectedly, the younger (3 month old) 3xTg-AD mice were as impaired in the spatial working memory task as were the older (8 month old) 3xTg-AD mice when compared with age-matched NonTg control animals. Field potential recordings from the CA1 region of slices prepared from the ventral hippocampus were obtained to assess synaptic transmission and capability for synaptic plasticity. At 3 months of age, the NMDA receptor-dependent component of LTP was reduced in 3xTg-AD mice. However, the magnitude of the non-NMDA receptor-dependent component of LTP was concomitantly increased, resulting in a similar amount of total LTP in 3xTg-AD and NonTg mice. At 8 months of age, the NMDA receptor-dependent LTP was again reduced in 3xTg-AD mice, but now the non-NMDA receptor-dependent component was decreased as well, resulting in a significantly reduced total amount of LTP in 3xTg-AD compared with NonTg mice. Both 3 and 8 month old 3xTg-AD mice exhibited reductions in paired-pulse facilitation and NMDA receptor-dependent LTP that coincided with the deficit in spatial working memory. The early presence of this cognitive impairment and the associated alterations in synaptic plasticity demonstrate that the onset of some behavioral and neurophysiological consequences can occur before the detectable presence of plaques and tangles in the 3xTg-AD mouse model of Alzheimer's disease.